Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
22 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
220 mg/m³
Explanation for the modification of the dose descriptor starting point:
In the absence of specific data for both the starting route (oral) and the end route (inhalation), worst case assumptions have to be made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL.
AF for dose response relationship:
1
Justification:
starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Toxicodynamic and toxicokinetic standard AF of 2.5 is not applicable because studies on different species and strains of rat with this substance have indicated no differences in susceptibility or toxic response between species.
AF for other interspecies differences:
1
Justification:
Toxicodynamic and toxicokinetic standard AF of 2.5 is not applicable because studies on different species and strains of rat with this substance have indicated no differences in susceptibility or toxic response between species.
AF for intraspecies differences:
5
Justification:
Worker default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
112.4 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
other: LOAEL
AF for dose response relationship:
1
Justification:
LOAEL, but only very minor effects seen in 1 animal at this dose so factor of 1 is applicable
AF for differences in duration of exposure:
1
Justification:
No AF greater than 1 required for duration because the acute and repeat dose dermal studies indicate that concentration rather than duration determines the irritant response
AF for interspecies differences (allometric scaling):
1
Justification:
AF not aplicable for local effects
AF for other interspecies differences:
1
Justification:
AF not aplicable for local effects
AF for intraspecies differences:
5
Justification:
worker default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.45 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Value:
109 mg/m³
Explanation for the modification of the dose descriptor starting point:
For potential inhalation exposure, route-to-route extrapolation from the oral NOAEL value of 250 mg/kg bw/day was performed. In the absence of specific data for both the starting route (oral) and the end route (inhalation), worst case assumptions have to be made. It was assumed that a limited absorption occurs by the oral route, leading to a low (conservative) internal NOAEL. To secure a conservative external NOAEL, a maximum absorption should be assumed for the inhalation route (i.e.; 100%) leading to a low external NOAEL
AF for dose response relationship:
1
Justification:
NOAEL starting point
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
1
Justification:
toxicodynamic and toxicokinetic standard AF of 2.5 is not applicable because studies on different species and strains of rat with this substance have indicated no differences in susceptibility or toxic response between species
AF for other interspecies differences:
1
Justification:
toxicodynamic and toxicokinetic standard AF of 2.5 is not applicable because studies on different species and strains of rat with this substance have indicated no differences in susceptibility or toxic response between species
AF for intraspecies differences:
10
Justification:
General population default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
56.2 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor:
other: LOAEL
AF for dose response relationship:
1
Justification:
LOAEL, but only very minor effects seen in 1 animal at this dose so factor of 1 is applicable
AF for differences in duration of exposure:
1
Justification:
No AF greater than 1 required for duration because the acute and repeat dose dermal studies indicate that concentration rather than duration determines the irritant response
AF for interspecies differences (allometric scaling):
1
Justification:
No AF greater than 1 required for duration because the acute and repeat dose dermal studies indicate that concentration rather than duration determines the irritant response
AF for other interspecies differences:
1
Justification:
No AF greater than 1 required for duration because the acute and repeat dose dermal studies indicate that concentration rather than duration determines the irritant response
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation required.
AF for dose response relationship:
1
Justification:
NOAEL starting point
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human (default)
AF for other interspecies differences:
2.5
Justification:
toxicodynamic and toxicokinetic (default)
AF for intraspecies differences:
10
Justification:
general population default
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population